- Email: [email protected]
Clinical outcome in hospitalized cirrhotic patients with bacterial infections treated with empirical or antibiogram-guided therapy
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Abstracts / Digestive and Liver Disease 48S (2016) e42–e64
(range 7–196). At baseline, NASH was diagnosed in 61.2%, significant and advanced fibrosis in 19.4% and 10.4% respectively. Overall, 15 patients (22%) had fibrosis progression, 42 (63%) had no change, whereas 10 (15%) had regression. There was no difference in FPR between patients with NASH and simple steatosis at baseline (0.08 ± 0.2 vs. 0.03 ± 0.4 units/year; p = 0.88). Age and sex did not influence FPR, whereas BMI was associated with faster FPR (p = 0.008). Diabetic patients showed faster FPR compared to non-diabetic (0.32 ± 0.6 vs. −0.02 ± 0.2; p = 0.04). Moreover, FPR was associated with elevated AST at baseline (>41 UI/l; p = 0.03). Interestingly, patients receiving renin–angiotensin–aldosterone axis modulators (RAAAM) for hypertension or diabetic kidney disease were less prone to fibrosis progression (−0.08 ± 0.16 vs. 0.07 ± 0.37; p = 0.018). AT multivariate analysis, FPR was associated with diabetes (estimate 0.183 ± 0.05; p < 0.001), higher BMI (estimate 0.014 ± 0.005; p = 0.008) and lack of treatment with RAAAM (estimate 0.104 ± 0.049; p = 0.038) independently of age, sex and AST. Conclusion: This study confirms in an Italian prospective cohort that NASH is not required for NAFLD progression, especially when diabetes and obesity are present. RAAAM may protect from fibrosis progression in NAFLD. http://dx.doi.org/10.1016/j.dld.2015.12.102 F-05 DIFFERENTIAL INFLAMMATORY PHENOTYPES UPON GENETIC OR PHARMACOLOGIC INACTIVATION OF INDOLEAMINE DIOXYGENASE IN EXPERIMENTAL STEATOHEPATITIS E. Vivoli 1 , B. Piombanti 1 , F. Fallarino 2 , F. Marra 1
with vehicle. Of note, no differences in myeloperoxidase expression were found in IDO-1 KO mice. Conclusions: Interference with the IDO pathway by 1-MT administration or by genetic deletion differentially affects the inflammatory phenotype of experimental steatohepatitis, involving neutrophilic recruitment. Metabolomic analysis is underway to dissect the components of the IDO pathway which are differentially affected by the two protocols. http://dx.doi.org/10.1016/j.dld.2015.12.103 F-06 CLINICAL OUTCOME IN HOSPITALIZED CIRRHOTIC PATIENTS WITH BACTERIAL INFECTIONS TREATED WITH EMPIRICAL OR ANTIBIOGRAM-GUIDED THERAPY G. Caccamo 1 , S. Maimone 1 , R. Filomia 1,2 , M.S. Franzè 3 , S. Tomeo 1,2 , R. Spinella 1,2 , T. Lembo 1,2 , A. Alibrandi 4 , P. Mondello 5 , C. Saitta 1 , I. Cacciola 1,2 , G. Squadrito 1,6 , G. Raimondo 1,2 1 Division of Clinical and Molecular Hepatology, University Hospital of Messina, Italy 2 Department of Clinical and Experimental Medicine, University Hospital of Messina, Italy 3 School of Medicine, Universiy of Messina, Italy 4 Department of Economics, University of Messina, Italy 5 Unit of Infectious Disease, University Hospital of Messina, Italy 6 Department of Human Pathology, University Hospital of Messina, Messina, Italy
1
Dipartimento di Medicina Sperimentale e Clinica, Università di Firenze, Italy 2 Dipartimento di Medicina Sperimentale, Università di Perugia, Italy Background and aims: The pathogenic mechanisms underlying development of nonalcoholic steatohepatitis are still elusive. Indoleamine 2,3-dioxygenase (IDO-1), an enzyme that mediates the catabolism of l-tryptophan to l-kynurenine, plays an important role in hepatic immune regulation, mediating inflammation or tolerance depending on the type of injury and the tissue involved. In the present study, we examined the effect of pharmacological or genetic inhibition of IDO-1 on the development of steatohepatitis induced by a methionine and choline-deficient (MCD) diet in mice. Methods: C57Bl/6 mice fed a MCD diet for 4 weeks, were treated with the specific IDO inhibitor, 1-methyl-d-triptophan (1MT, 5 mg/ml) or its vehicle in drinking water. In separate experiments, WT and IDO-1 KO C57Bl/6 mice were fed MCD or its control for 4 weeks. Intrahepatic gene expression was assayed by quantitative real time PCR. Results: No differences in ALT levels were observed comparing mice receiving MCD and pharmacological or genetic interference with IDO-1. Genetic IDO-1 deletion resulted in significantly milder inflammatory phenotype in mice receiving the MCD diet, as indicated by reduced intrahepatic gene expression of proinflammatory factors, including CD11b, CCL2, IL-1 beta and iNOS, and by a lower necroinflammation score. In contrast, pharmacological inhibition of IDO by 1-MT was associated with more severe necroinflammation and increased expression of genes related to inflammatory cell infiltration. Of note, in mice receiving the MCD diet and 1-MT, expression of myeloperoxidase, an index of neutrophilic infltration, was significantly higher compared to mice receiving MCD
Aim of this study was to evaluate short-term mortality in a cohort of cirrhotic patients treated with empirical versus antibiogram-guided antibiotic therapy. We retrospectively evaluated 200 bacterial infection (BI) episodes occurring in 186 cirrhotics [56.5% male; mean age 65.8 ± 12.1 years; 45 with hepatocellular carcinoma (HCC); ChildPugh (CP) classes A/B/C: 41/108/51; MELD score: 14.2 ± 7.3] consecutively hospitalized from January 2009 to March 2015. Microbiological cultures were performed before starting empirical antibiotic treatment (EAT) in all the cases. Therapy was modified both in patients with positive cultures (Cpos) according to antibiogram and in patients with negative cultures (Cneg) with clinical or laboratory evidence of EAT inefficacy. Mortality was evaluated at 1 month (M-1) and 3 months (M-3) after starting EAT. Cultures tested positive in 111/200 BI episodes (55.5%). Bacterial isolated were Gram-negative in 48.8%, Gram-positive in 42.6%, mixed in 8.6%. EAT was changed in 37/111 (33.3%) Cpos and in 35/89 (39.3%) Cneg BI episodes (p = 0.5). Overall mortality at M-1 and M-3 was 17% and 26.5%, respectively, being significantly higher in Cneg than in Cpos patients (M-1: 25.8%Cneg vs 9.9%Cpos, p = 0.001; M-3: 38.2%Cneg vs 17.1%Cpos, p = 0.008)]. At Cox-regression analysis, independent risk factors for M-1 mortality were: HCC (HR: 2.93, 95%CI: 1.46–5.89, p = 0.003); higher CP score (HR: 2.22, 95%CI: 1.21–4.06, p = 0.01); creatinine (HR:1.64, 95%CI: 1.27–2.13, p = 0.0001); C-reactive protein (CRP) (HR: 1.11, 95%CI: 1.01–1.22, p = 0.036); Cneg (HR: 0.46, 95%CI: 0.22–0.98, p = 0.045). Creatinine, CRP and Cneg were significant risk factors of mortality also when HCC was excluded. M-3 mortality risk factors were: HCC (HR: 2.42, 95%CI: 1.36–4.3, p = 0.003); creatinine (HR: 1.37, 95%CI: 1.06–1.76, p = 0.016); sodium (HR: 0.94, 95%CI: 0.89–0.99, p = 0.041); Cneg (HR: 0.54, 95%CI: 0.3–0.98, p = 0.044). When HCC
Abstracts / Digestive and Liver Disease 48S (2016) e42–e64
patients were excluded from the analysis, risk factors of mortality were Cneg, diabetes and lenght of stay. In conclusion cirrhotics with BI and negative microbiological cultures have a significantly higher mortality rate compared to cirrhotics with positive cultures, and this independently of HCC co-existence. http://dx.doi.org/10.1016/j.dld.2015.12.104 F-07 FUNCTIONALIZED POLYMERS TO TARGET SERPINB3 IN HEPATOMA CELLS S. Quarta 1 , S. Chiarani 2 , J. Baseggio 2 , P. Pontisso 1 , P. Caliceti 2 1
Dept of Medicine, Internal Medicine and Hepatology, Regional Center for Hepatology (RCH), University of Padua, Italy 2 Dept of Pharmacological and Pharmaceutical Sciences, University of Padua, Italy Introduction: Natural polysaccharides are suitable candidates for the design of novel biomaterials, because they are non-toxic and biodegradable. Pullulan is a polysaccharide widely exploited for biomedical and pharmaceutical applications. N-terminal PreS1 sequence of HBV has been shown to bind with high affinity SerpinB3, a molecule highly expressed in hepatocellular carcinomas with poor prognosis, but not in normal hepatocytes. Aim: To functionalize the polysaccaridic system with the targeting PreS1 sequence for new therapeutic approaches in liver cancer. Materials and methods: The fluorescent module (PEGrhodamine, PEG-Rho) and the targeting moiety (PEG-PreS1) were linked to oxidized Pullulan (Pull) to give the final Pull-preS1 reagent. Pullulan without PreS1 (Pull-Rho) was synthesized as negative control. HepG2 cells stably transfected with SerpinB3 or with the plasmid vector alone, as control, were treated with different concentrations (2–200 mg/ml) of PreS1- and control-bioconjugates for 0–4 h. The uptake of the nanosystems was assessed by cytofluorimetric and fluorescence analysis, while their cytotoxicity was analyzed using the xCELLigence instrument. Results: The cytofluorimetic analysis documented a significant selective binding of Pull-Rho-PreS1 (1:200) to SerpinB3 expressing cells at 200 mg/ml concentration and 4 h incubation. These findings were confirmed by immunofluorescence. No cytotoxicity of the compounds was observed by the real-time xCELLigence vitality assay in these optimal conditions. Conclusions: A new functionalized polysaccaridic system using Pullulan and PreS1 as targeting sequence has been developed. This compound might become a useful tool for imaging and drug delivery in HCC expressing SerpinB3. http://dx.doi.org/10.1016/j.dld.2015.12.105
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F-08 SORAFENIB IN CLINICAL PRACTICE: POOLED ANALYSIS OF TWO PROSPECTIVE OBSERVATIONAL STUDIES IN HEPATOCELLULAR CARCINOMA (HCC) G.G. Di Costanzo 1 , S. D’Angelo 2 , T. Zolfino 3 , V. Lorusso 4 , V. Montesarchio 5 , G. de Stefano 5 , R. Sacco 6 , A.F. Attili 7 , A. Benedetti 8 , D. Sansonno 9 , L. Giannitrapani 10 , A. Buonadonna 11 , P. Giovanis 12 , G. Cabibbo 13 , F. De Vita 14 , P. Carucci 15 , M. Pirisi 16 , M. Moscovici 17 , S. Pisconti 18 , B. Daniele 19 1
Ospedale Cardarelli, Napoli, Italy AO San Giuseppe Moscati, Avellino, Italy 3 AO G. Brotzu, Cagliari, Italy 4 IRCCS Ospedale di Bari, Bari, Italy 5 AORN AO dei Colli Monaldi-Cotugno CTO, Napoli, Italy 6 AOU-Pisana, Ospedale Cisanello, Pisa, Italy 7 Azienda Policlinico Umberto I, Roma, Italy 8 AOU Ospedali Riuniti, PO Umberto I, Torrette di Ancona, Ancona, Italy 9 AOU Policlinico Consorziale di Bari G. Bacelli, Bari, Italy 10 AOUP Paolo Giaccone, Palermo, Italy 11 Centro di Riferimento Oncologico CRO, Aviano, Italy 12 Azienda U.L.S.S. n. 2 di Feltre, Feltre (BL), Italy 13 Policlinico Giaccone-Università degli Studi, Palermo, Italy 14 Oncologia Medica Seconda Università di Napoli, Napoli, Italy 15 Ospedale Le Molinette, Torino, Italy 16 AOU Maggiore della Carità, Novara, Italy 17 Bayer SpA, Milano, Italy 18 Ospedale S.G. Moscati, Taranto, Italy 19 AO Gaetano Rummo, Benevento, Italy 2
Introduction: Sorafenib is the recommended standard of care in HCC patients with preserved liver function who are ineligible or have failed surgical or loco-regional treatments. Aim: Characterize efficacy and safety of sorafenib in routine clinical practice in Italian centers. Materials and methods: Data from the Italian subgroup of GIDEON (international study) and from STELLA (Italian study), two prospective observational studies were pooled. Efficacy and safety of sorafenib were primary objectives in the two studies. Eligible patients were those for whom the decision to treat with sorafenib has been made prior to enrollment. Results: Between June 2009 and January 2014, 512 patients were enrolled in both studies of which 498 were valid for efficacy and 485 for safety analysis. Demographic characteristics: male 81%, median age 70 y (range 28–90) and >26% 75 y or above. Etiology: hepatitis C in 55% and hepatitis B in 20% of patients. The majority (62%) had ECOG PS 0 and Child-Pugh A/B/C was present in 79/13/1% respectively. More than half of patients were BCLC stage C (58%) whereas BCLC B and BCLC A accounted for 31% and 9% respectively. Overall incidence of adverse events-(AE) (all grades) was 82%. The most frequent were fatigue (29%), diarrhea (24%) and hand-foot skin reaction (16%). Incidence of AEs resulting in permanent discontinuation (drug-related or not) was 32%. Median overall survival was 10.7 [95%CI: 9.3–12.7] months and median time to progression was 6 [95%CI: 5.2–7.0] months.
Abstracts / Digestive and Liver Disease 48S (2016) e42–e64
(range 7–196). At baseline, NASH was diagnosed in 61.2%, significant and advanced fibrosis in 19.4% and 10.4% respectively. Overall, 15 patients (22%) had fibrosis progression, 42 (63%) had no change, whereas 10 (15%) had regression. There was no difference in FPR between patients with NASH and simple steatosis at baseline (0.08 ± 0.2 vs. 0.03 ± 0.4 units/year; p = 0.88). Age and sex did not influence FPR, whereas BMI was associated with faster FPR (p = 0.008). Diabetic patients showed faster FPR compared to non-diabetic (0.32 ± 0.6 vs. −0.02 ± 0.2; p = 0.04). Moreover, FPR was associated with elevated AST at baseline (>41 UI/l; p = 0.03). Interestingly, patients receiving renin–angiotensin–aldosterone axis modulators (RAAAM) for hypertension or diabetic kidney disease were less prone to fibrosis progression (−0.08 ± 0.16 vs. 0.07 ± 0.37; p = 0.018). AT multivariate analysis, FPR was associated with diabetes (estimate 0.183 ± 0.05; p < 0.001), higher BMI (estimate 0.014 ± 0.005; p = 0.008) and lack of treatment with RAAAM (estimate 0.104 ± 0.049; p = 0.038) independently of age, sex and AST. Conclusion: This study confirms in an Italian prospective cohort that NASH is not required for NAFLD progression, especially when diabetes and obesity are present. RAAAM may protect from fibrosis progression in NAFLD. http://dx.doi.org/10.1016/j.dld.2015.12.102 F-05 DIFFERENTIAL INFLAMMATORY PHENOTYPES UPON GENETIC OR PHARMACOLOGIC INACTIVATION OF INDOLEAMINE DIOXYGENASE IN EXPERIMENTAL STEATOHEPATITIS E. Vivoli 1 , B. Piombanti 1 , F. Fallarino 2 , F. Marra 1
with vehicle. Of note, no differences in myeloperoxidase expression were found in IDO-1 KO mice. Conclusions: Interference with the IDO pathway by 1-MT administration or by genetic deletion differentially affects the inflammatory phenotype of experimental steatohepatitis, involving neutrophilic recruitment. Metabolomic analysis is underway to dissect the components of the IDO pathway which are differentially affected by the two protocols. http://dx.doi.org/10.1016/j.dld.2015.12.103 F-06 CLINICAL OUTCOME IN HOSPITALIZED CIRRHOTIC PATIENTS WITH BACTERIAL INFECTIONS TREATED WITH EMPIRICAL OR ANTIBIOGRAM-GUIDED THERAPY G. Caccamo 1 , S. Maimone 1 , R. Filomia 1,2 , M.S. Franzè 3 , S. Tomeo 1,2 , R. Spinella 1,2 , T. Lembo 1,2 , A. Alibrandi 4 , P. Mondello 5 , C. Saitta 1 , I. Cacciola 1,2 , G. Squadrito 1,6 , G. Raimondo 1,2 1 Division of Clinical and Molecular Hepatology, University Hospital of Messina, Italy 2 Department of Clinical and Experimental Medicine, University Hospital of Messina, Italy 3 School of Medicine, Universiy of Messina, Italy 4 Department of Economics, University of Messina, Italy 5 Unit of Infectious Disease, University Hospital of Messina, Italy 6 Department of Human Pathology, University Hospital of Messina, Messina, Italy
1
Dipartimento di Medicina Sperimentale e Clinica, Università di Firenze, Italy 2 Dipartimento di Medicina Sperimentale, Università di Perugia, Italy Background and aims: The pathogenic mechanisms underlying development of nonalcoholic steatohepatitis are still elusive. Indoleamine 2,3-dioxygenase (IDO-1), an enzyme that mediates the catabolism of l-tryptophan to l-kynurenine, plays an important role in hepatic immune regulation, mediating inflammation or tolerance depending on the type of injury and the tissue involved. In the present study, we examined the effect of pharmacological or genetic inhibition of IDO-1 on the development of steatohepatitis induced by a methionine and choline-deficient (MCD) diet in mice. Methods: C57Bl/6 mice fed a MCD diet for 4 weeks, were treated with the specific IDO inhibitor, 1-methyl-d-triptophan (1MT, 5 mg/ml) or its vehicle in drinking water. In separate experiments, WT and IDO-1 KO C57Bl/6 mice were fed MCD or its control for 4 weeks. Intrahepatic gene expression was assayed by quantitative real time PCR. Results: No differences in ALT levels were observed comparing mice receiving MCD and pharmacological or genetic interference with IDO-1. Genetic IDO-1 deletion resulted in significantly milder inflammatory phenotype in mice receiving the MCD diet, as indicated by reduced intrahepatic gene expression of proinflammatory factors, including CD11b, CCL2, IL-1 beta and iNOS, and by a lower necroinflammation score. In contrast, pharmacological inhibition of IDO by 1-MT was associated with more severe necroinflammation and increased expression of genes related to inflammatory cell infiltration. Of note, in mice receiving the MCD diet and 1-MT, expression of myeloperoxidase, an index of neutrophilic infltration, was significantly higher compared to mice receiving MCD
Aim of this study was to evaluate short-term mortality in a cohort of cirrhotic patients treated with empirical versus antibiogram-guided antibiotic therapy. We retrospectively evaluated 200 bacterial infection (BI) episodes occurring in 186 cirrhotics [56.5% male; mean age 65.8 ± 12.1 years; 45 with hepatocellular carcinoma (HCC); ChildPugh (CP) classes A/B/C: 41/108/51; MELD score: 14.2 ± 7.3] consecutively hospitalized from January 2009 to March 2015. Microbiological cultures were performed before starting empirical antibiotic treatment (EAT) in all the cases. Therapy was modified both in patients with positive cultures (Cpos) according to antibiogram and in patients with negative cultures (Cneg) with clinical or laboratory evidence of EAT inefficacy. Mortality was evaluated at 1 month (M-1) and 3 months (M-3) after starting EAT. Cultures tested positive in 111/200 BI episodes (55.5%). Bacterial isolated were Gram-negative in 48.8%, Gram-positive in 42.6%, mixed in 8.6%. EAT was changed in 37/111 (33.3%) Cpos and in 35/89 (39.3%) Cneg BI episodes (p = 0.5). Overall mortality at M-1 and M-3 was 17% and 26.5%, respectively, being significantly higher in Cneg than in Cpos patients (M-1: 25.8%Cneg vs 9.9%Cpos, p = 0.001; M-3: 38.2%Cneg vs 17.1%Cpos, p = 0.008)]. At Cox-regression analysis, independent risk factors for M-1 mortality were: HCC (HR: 2.93, 95%CI: 1.46–5.89, p = 0.003); higher CP score (HR: 2.22, 95%CI: 1.21–4.06, p = 0.01); creatinine (HR:1.64, 95%CI: 1.27–2.13, p = 0.0001); C-reactive protein (CRP) (HR: 1.11, 95%CI: 1.01–1.22, p = 0.036); Cneg (HR: 0.46, 95%CI: 0.22–0.98, p = 0.045). Creatinine, CRP and Cneg were significant risk factors of mortality also when HCC was excluded. M-3 mortality risk factors were: HCC (HR: 2.42, 95%CI: 1.36–4.3, p = 0.003); creatinine (HR: 1.37, 95%CI: 1.06–1.76, p = 0.016); sodium (HR: 0.94, 95%CI: 0.89–0.99, p = 0.041); Cneg (HR: 0.54, 95%CI: 0.3–0.98, p = 0.044). When HCC
Abstracts / Digestive and Liver Disease 48S (2016) e42–e64
patients were excluded from the analysis, risk factors of mortality were Cneg, diabetes and lenght of stay. In conclusion cirrhotics with BI and negative microbiological cultures have a significantly higher mortality rate compared to cirrhotics with positive cultures, and this independently of HCC co-existence. http://dx.doi.org/10.1016/j.dld.2015.12.104 F-07 FUNCTIONALIZED POLYMERS TO TARGET SERPINB3 IN HEPATOMA CELLS S. Quarta 1 , S. Chiarani 2 , J. Baseggio 2 , P. Pontisso 1 , P. Caliceti 2 1
Dept of Medicine, Internal Medicine and Hepatology, Regional Center for Hepatology (RCH), University of Padua, Italy 2 Dept of Pharmacological and Pharmaceutical Sciences, University of Padua, Italy Introduction: Natural polysaccharides are suitable candidates for the design of novel biomaterials, because they are non-toxic and biodegradable. Pullulan is a polysaccharide widely exploited for biomedical and pharmaceutical applications. N-terminal PreS1 sequence of HBV has been shown to bind with high affinity SerpinB3, a molecule highly expressed in hepatocellular carcinomas with poor prognosis, but not in normal hepatocytes. Aim: To functionalize the polysaccaridic system with the targeting PreS1 sequence for new therapeutic approaches in liver cancer. Materials and methods: The fluorescent module (PEGrhodamine, PEG-Rho) and the targeting moiety (PEG-PreS1) were linked to oxidized Pullulan (Pull) to give the final Pull-preS1 reagent. Pullulan without PreS1 (Pull-Rho) was synthesized as negative control. HepG2 cells stably transfected with SerpinB3 or with the plasmid vector alone, as control, were treated with different concentrations (2–200 mg/ml) of PreS1- and control-bioconjugates for 0–4 h. The uptake of the nanosystems was assessed by cytofluorimetric and fluorescence analysis, while their cytotoxicity was analyzed using the xCELLigence instrument. Results: The cytofluorimetic analysis documented a significant selective binding of Pull-Rho-PreS1 (1:200) to SerpinB3 expressing cells at 200 mg/ml concentration and 4 h incubation. These findings were confirmed by immunofluorescence. No cytotoxicity of the compounds was observed by the real-time xCELLigence vitality assay in these optimal conditions. Conclusions: A new functionalized polysaccaridic system using Pullulan and PreS1 as targeting sequence has been developed. This compound might become a useful tool for imaging and drug delivery in HCC expressing SerpinB3. http://dx.doi.org/10.1016/j.dld.2015.12.105
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F-08 SORAFENIB IN CLINICAL PRACTICE: POOLED ANALYSIS OF TWO PROSPECTIVE OBSERVATIONAL STUDIES IN HEPATOCELLULAR CARCINOMA (HCC) G.G. Di Costanzo 1 , S. D’Angelo 2 , T. Zolfino 3 , V. Lorusso 4 , V. Montesarchio 5 , G. de Stefano 5 , R. Sacco 6 , A.F. Attili 7 , A. Benedetti 8 , D. Sansonno 9 , L. Giannitrapani 10 , A. Buonadonna 11 , P. Giovanis 12 , G. Cabibbo 13 , F. De Vita 14 , P. Carucci 15 , M. Pirisi 16 , M. Moscovici 17 , S. Pisconti 18 , B. Daniele 19 1
Ospedale Cardarelli, Napoli, Italy AO San Giuseppe Moscati, Avellino, Italy 3 AO G. Brotzu, Cagliari, Italy 4 IRCCS Ospedale di Bari, Bari, Italy 5 AORN AO dei Colli Monaldi-Cotugno CTO, Napoli, Italy 6 AOU-Pisana, Ospedale Cisanello, Pisa, Italy 7 Azienda Policlinico Umberto I, Roma, Italy 8 AOU Ospedali Riuniti, PO Umberto I, Torrette di Ancona, Ancona, Italy 9 AOU Policlinico Consorziale di Bari G. Bacelli, Bari, Italy 10 AOUP Paolo Giaccone, Palermo, Italy 11 Centro di Riferimento Oncologico CRO, Aviano, Italy 12 Azienda U.L.S.S. n. 2 di Feltre, Feltre (BL), Italy 13 Policlinico Giaccone-Università degli Studi, Palermo, Italy 14 Oncologia Medica Seconda Università di Napoli, Napoli, Italy 15 Ospedale Le Molinette, Torino, Italy 16 AOU Maggiore della Carità, Novara, Italy 17 Bayer SpA, Milano, Italy 18 Ospedale S.G. Moscati, Taranto, Italy 19 AO Gaetano Rummo, Benevento, Italy 2
Introduction: Sorafenib is the recommended standard of care in HCC patients with preserved liver function who are ineligible or have failed surgical or loco-regional treatments. Aim: Characterize efficacy and safety of sorafenib in routine clinical practice in Italian centers. Materials and methods: Data from the Italian subgroup of GIDEON (international study) and from STELLA (Italian study), two prospective observational studies were pooled. Efficacy and safety of sorafenib were primary objectives in the two studies. Eligible patients were those for whom the decision to treat with sorafenib has been made prior to enrollment. Results: Between June 2009 and January 2014, 512 patients were enrolled in both studies of which 498 were valid for efficacy and 485 for safety analysis. Demographic characteristics: male 81%, median age 70 y (range 28–90) and >26% 75 y or above. Etiology: hepatitis C in 55% and hepatitis B in 20% of patients. The majority (62%) had ECOG PS 0 and Child-Pugh A/B/C was present in 79/13/1% respectively. More than half of patients were BCLC stage C (58%) whereas BCLC B and BCLC A accounted for 31% and 9% respectively. Overall incidence of adverse events-(AE) (all grades) was 82%. The most frequent were fatigue (29%), diarrhea (24%) and hand-foot skin reaction (16%). Incidence of AEs resulting in permanent discontinuation (drug-related or not) was 32%. Median overall survival was 10.7 [95%CI: 9.3–12.7] months and median time to progression was 6 [95%CI: 5.2–7.0] months.